Hexa-arm polyethylene glycol and its derivatives and the methods of preparation thereof

Abstract

The present invention relates to novel hexa-arm polyethylene glycol (6-arm PEG) and its derivatives. The core of 6-arm PEG derivatives is sorbitol and the end groups can be derivatized into many different reactive functionalities that are useful in conjugating with many different targets. The present invention also provides a biodegradable polymeric hydrogel-forming composition comprising the 6-arm PEG and its derivatives, and methods of using such 6-arm PEG derivatives as surgical or biological implants or sealants.

1. A novel hexa-arm polyethylene glycol (6-arm PEG) compound and its derivatives represented by the following formula (I): 
                 
 
       wherein,
 R 1  is a hydrogen atom, a hydroxyl group, alkyl group having 1 to 5 carbon atoms, an acrylate group, an acetaldehyde group, an epoxide group, a hydrazide group, a tresylate group, an alkylcarbonyl group or a phenylcarbonyl group having 1 to 10 carbon atoms which substituted by nitro group, primary, secondary or tertiary silane group which substituted by alkyl or alkoxy group having 1 to 5 carbon atoms, glutaric acid group, succinic acid group or CO(CH 2 ) m COONHS, m is an integer of 2 to 3, n is an integer of 20 to 2500.  
 
     
     
       2. The compound of  claim 1 , which is one selected from the group of consisting of
 6-arm PEG-succinic acid (6-arm PEG-SA),  
 6-arm PEG-glutaric acid (6-arm PEG-GA),  
 6-arm PEG-succimidyl succinate (6-arm PEG-SS),  
 6-arm PEG-succimidyl glutarate (6-arm PEG-SG),  
 6-arm PEG-nitrophenyl carbonate (6-arm PEG-NPC),  
 6-arm PEG-silane,  
 6-arm PEG-acrylate,  
 6-arm PEG-hydrazide,  
 6-arm PEG-tresylate,  
 6-arm PEG-propion aldehyde,  
 6-arm PEG-tosylate.  
 
     
     
       3. A novel hexa-arm PEG compound and its derivatives represented by the following formula (II): 
                 
 
       wherein,
 R 2  is a hydrogen atom, a hydroxyl group, an isocyanate group, a maleimide group, a o-pyridyl disulfide group, an alkylsulfonyl, an arylsulfonyl or a vinylsulfonyl group having 1 to 5 carbon atoms, or an alkyl or an alkene group having 1 to 5 carbon atoms which is substituted or not substituted by an amine group, n is an integer of 20 to 2500.  
 
     
     
       4. The compound of  claim 3 , which is one selected from the group of consisting of
 6-arm PEG-isocyanate,  
 6-arm PEG-maleimide,  
 6-arm PEG-orthopyridyl disulfide,  
 6-arm PEG-vinylsulfone,  
 6-arm PEG-amine (6-arm PEG-NH 2 ),  
 6-arm PEG-thiol (6-arm PEG-SH).